Mg-Based Magnetic Hydrogel Activate Immuno-Response For Hnscc Therapy

HNSCC is the most common tumor in the head and neck region, and its traditional therapy involves surgical resection, radiotherapy, and chemotherapy, but there are many problems in clinical practice. Recently, scholars from both domestic and abroad focus on exploring novel biomedical metallic materials for clinical use in HNSCC. This study aims to develop Mg-based hydrogel with magnetical property and then elucidate its anti-tumor function and relevant mechanism. Fe3O4 magnetic nanoparticles are integrated into Mg@Gel via sol-gel assembly to create Mg-Gel@Fe3O4. Physicochemical examinations include SEM-EDS, dynamic rheology, VSM and magnetic hyperthermia tests. In vitro mechanisms are studied via proliferation and toxicity assays, pH tracking, MMP disruption, ROS detection, ELISA and immunofluorescence. Mouse models of tumor-bearing and ICD vaccination, combined with lentivirus and CRISPR-Cas9 technologies, elucidate its immunomodulatory effects and ICD pathways. We develop Mg-Gel@Fe3O4 with magnetothermal and chemodynamic effects. Mg-Gel@Fe3O4 can trigger ICD via ROS accumulation, MMP collapse and intracellular pH imbalance. Mg-Gel@Fe3O4 can also improve CD4+/CD8+ T cell infiltration into the tumor microenvironment and upregulate TNF-α and IFN-γ, remodeling HNSCC from the immunosuppressive phenotype into the immunogenic phenotype. Specifically, Mg-Gel@Fe3O4 can induce ICD of tumor cells via regulating LTF, and thereby kill HNSCC primary tumors and distal lesions. Mg-Gel@Fe3O4 can induce ICD of tumor cells via regulating LTF, and thereby kill HNSCC primary tumors and distal lesions. These findings provide novel strategies for biomedical metallic materials in tumor therapy.